MOPE237 - Poster Exhibition
Safety and efficacy of maraviroc (MVC) in CCR5-tropic HIV-1-infected children aged 2 to < 18 years
C. Giaquinto1, J. Fourie2, I. Mitha3, A. Fang4, M. Vourvahis5, L. McFadyen6, S.R. Valluri4, C. Craig6, G. Mukwaya4, H. Valdez4, J. Heera5
1University of Padova, Pediatrics Department, Padova, Italy, 2Dr. J Fourie Medical Centre, Dundee, South Africa, 3Benmed Clinic, Benoni, Gauteng, South Africa, 4Pfizer, Inc., New York, United States, 5Pfizer, Inc., New London, United States, 6Pfizer, Sandwich, United Kingdom
Background: Maraviroc (MVC) is a CCR5 antagonist, approved to treat adults infected with CCR5-tropic HIV-1 but not yet approved for pediatric use.
Methods: This is an open-label, two-stage (stage 1: dose-finding; stage 2: safety/efficacy evaluation), age-stratified, non-comparative, multi-center study to evaluate safety, tolerability, and pharmacokinetics of MVC plus optimized background therapy (OBT) in treatment-experienced children. Subjects infected with CCR5-tropic HIV-1 are enrolled into one of four age/formulation cohorts (table).
Results: Thirty-one subjects were enrolled by 08/27/2010, initially dosed according to body surface area and OBT interactions with MVC. Dose adjustment occurred if average concentrations < 100 ng/mL at Week 2. Maintenance MVC doses ranged from 50-450 mg BID.
|Subject Characteristics||Cohort 1:
³2 - <6 years Liquid MVC
³6 - <12 years
³6 - <12 years
³12 - <18 years
|Sex (Males/Females)||2 / 0||5 / 7||3 / 2||4 / 8|
|Race (White/Black/Asian)||0 / 0 / 2||3 / 8 / 1||1 / 4 / 0||4 / 6 / 2|
|Median treatment duration (days)||200||341||322||166|
CD4+ counts (µ/L)||151||478||192||312|
Five subjects had six treatment-emergent, non-treatment-related serious adverse events (AEs): uncontrolled behavior, prurigo, pneumonia, gastrocutaneous fistula, H1N1 infection, and pulmonary tuberculosis. Five subjects experienced 11 treatment-related AEs (all ≤Grade-2): vomiting, elevated liver enzymes, nightmares, cardiac murmur, prurigo, abdominal pain, skin rash, decreased appetite, dizziness (2), and depression. Eight subjects had nine Grade-3 abnormal laboratory results: hyponatremia (4), neutropenia (4), and hypercholesterolemia (1). No deaths or discontinuations due to AEs occurred. HIV RNA < 48 copies/mL was achieved in 13/20 (65%) and 6/9 (67%) patients at Weeks 24 and 48, respectively. Eight subjects discontinued; four with virologic failure without tropism change or MVC resistance at failure time, but with pharmacokinetic evidence of poor adherence.
Conclusion: Preliminary data suggest that MVC plus OBT in treatment-experienced children was safe, well tolerated, and effective. Enrollment is continuing.
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